SLU-PP-332 and the ERR Agonist Family: A Research Review of GSK4716, DY131, SLU-PP-915 and the Catalogue Nomenclature Behind the "Peptide" Label

By Peptide Insider Research Team · 12 min read · Last updated September 11, 2026

SLU-PP-332 is a synthetic acylhydrazone agonist of the estrogen-related receptors (ERRα, ERRβ and ERRγ) that is almost universally listed in research catalogues under headings such as slu pp 332 peptide, slu-pp-332 peptide or simply slupp332 — even though it contains no amino acids and is not a peptide. This review addresses the classification problem directly, places SLU-PP-332 within the family of small-molecule ERR ligands from which it was derived (GSK4716, DY131, the inverse agonist XCT790 and the orally active successor SLU-PP-915), and tabulates the notation variants a researcher will encounter when comparing catalogue entries. All content is provided strictly for research reference.

Introduction

Few research compounds illustrate the gap between chemical identity and commercial taxonomy as clearly as SLU-PP-332. It was reported in 2023 as a chemical probe for the estrogen-related receptors, a subfamily of orphan nuclear receptors that govern mitochondrial biogenesis and oxidative metabolism [1]. Because its rodent phenotype — an ERRα-dependent transcriptional signature resembling acute aerobic exercise — drew the audience that follows research peptides, suppliers indexed it beside MOTS-c and AOD-9604, and the label "peptide" attached itself in queries and catalogue titles [1,3].

Our earlier SLU-PP-332 research review covered the mechanism and preclinical evidence base in depth. This companion article has a narrower purpose: to establish what SLU-PP-332 is chemically, to situate it within the two-decade lineage of synthetic ERR ligands that preceded and followed it, and to document how the same molecule appears under more than twenty different notations. Forms such as slu-pp, slupp, slupp 332 and sloop 332 are orthographic variants, not distinct analogs.

Chemical classification: why SLU-PP-332 is not a peptide

A peptide is a chain of amino acids joined by amide (peptide) bonds. SLU-PP-332 contains a single amide-like carbonyl, but it is part of a hydrazide (–C(=O)–NH–N=CH–) linking a 4-hydroxybenzoyl group to a 2-naphthaldehyde-derived imine; no α-amino acid residue is present anywhere in the structure [2]. With a molecular weight of 290.3 g/mol it is smaller than most dipeptides and falls squarely within conventional small-molecule drug-like space [2].

The mechanistic consequence is equally categorical. Signaling peptides such as ipamorelin or BPC-157 act at cell-surface receptors or extracellular targets; SLU-PP-332 diffuses into the nucleus and binds the ligand-binding domain of a transcription factor [1]. Its closest structural relatives are the phenolic acyl hydrazones described in 2005 as the first synthetic ERRβ/γ agonists [4]. The "peptide" suffix in queries such as slu pp 332 peptides or peptide slu-pp-332 is a catalogue convention and carries no chemical meaning.

Biological background: the ERR subfamily and its ligands

The estrogen-related receptors were the first orphan nuclear receptors to be cloned, identified through sequence similarity to the estrogen receptor although they do not bind estradiol [5]. Rather than being activated by a circulating hormone, ERRs are constitutively active and their transcriptional output is set by the abundance of PGC-1α and PGC-1β coactivators, which function as protein "ligands" [5]. In oxidative tissues — heart, skeletal muscle, kidney and brown adipose — the ERR/PGC-1 axis drives gene networks for mitochondrial biogenesis, the tricarboxylic acid cycle, oxidative phosphorylation and fatty-acid β-oxidation [5,6]. ERRα also directs PPARα signaling and fatty-acid handling genes in heart and skeletal muscle [6].

Because this is the same circuitry that endurance training remodels, ERRs became a natural target for what Fan and Evans termed "exercise mimetics" — pharmacological agents intended to reproduce specific transcriptional adaptations of exercise in skeletal muscle [7]. ERRα was long considered poorly druggable, and its first useful synthetic ligand, XCT790, was an inverse agonist [8]. Agonists for the subfamily arrived first for ERRβ and ERRγ, in the form of GSK4716 and DY131 [4,9]. SLU-PP-332 was reported as the first synthetic compound with meaningful ERRα agonism, derived by modifying the GSK4716 scaffold [1].

Structure–activity relationships across the ERR agonist family

All three published ERR agonist chemotypes share the 4-hydroxybenzohydrazide "left-hand" fragment; they differ in the aryl aldehyde used to form the imine. GSK4716 carries a 4-isopropylbenzylidene group and behaves as a selective ERRβ/γ agonist that mimics PGC-1α recruitment in cell-based assays with little activity at the classical estrogen receptors [4]. DY131 (also catalogued as GSK9089) substitutes a 4-(diethylamino)benzylidene group and is likewise ERRβ/γ selective, with no reported effect on ERRα, ERα or ERβ [9]. Crystal structures of the ERRγ ligand-binding domain with GSK4716 showed the acyl hydrazone stabilizing the active, coactivator-competent conformation [10].

SLU-PP-332 replaces the substituted phenyl ring with a 2-naphthyl group. The additional ring extends into the ERRα pocket and confers pan-agonism, with reported reporter-assay EC₅₀ values of approximately 98 nM (ERRα), 230 nM (ERRβ) and 430 nM (ERRγ) [1,2]. Downstream, the compound increases recruitment of PGC-1α/β, upregulates Ddit4, Pdk4 and electron-transport-chain genes, and in mouse skeletal muscle induces an ERRα-dependent program that overlaps with the transcriptional response to a single bout of aerobic exercise [1]. SLU-PP-915, disclosed in 2024, was produced by structure-based design to retain pan-ERR agonism while gaining oral bioavailability, a property SLU-PP-332 lacks [11].

XCT790, the ERRα inverse agonist often used as a control, also acts as a nanomolar mitochondrial uncoupler independently of ERRα, which complicates its interpretation [8,12].

Nomenclature and catalogue variants

The designation SLU-PP-332 encodes the institution (Saint Louis University), a program prefix (PP) and a compound serial number (332). None of the three elements is a chemical descriptor, and the hyphens are frequently dropped, spaced or mis-typed. The following variants were compiled from catalogue titles and search-engine query logs; every row refers to the same molecule, CAS 303760-60-3 [2].

Catalogue / query notation	Form	Interpretation
slu pp 332 peptide, slu-pp-332 peptide, slu pp-332 peptide, slu-pp 332 peptide	Spaced or hyphenated designation + "peptide"	Standard designation with the catalogue-class suffix; the compound is a small molecule, not a peptide
slupp332, slupp332 peptide, slupp 332, slupp, slupp peptide	Hyphens removed	Concatenated designation; "slupp" alone is an abbreviation with no other referent in the ERR literature
slu-pp, slu pp332, slu-pp 332	Partial or mixed spacing	Truncated or partially hyphenated designation
sloop peptide, sloop 332, sloup 332	Phonetic spelling	"SLU-PP" read aloud as "sloop"; a transcription of the spoken designation
slupe 332, slup 332, slup pp 332	Typographic	Dropped or transposed letters within the prefix
slu pp 322	Digit transposition	Serial number mis-typed; SLU-PP-322 is not a published ERR ligand
slu pp 332 peptides, peptide slu-pp-332	Plural / inverted word order	Query-form variants of the standard designation
SLU-PP-915	Distinct compound	Orally bioavailable successor pan-agonist — not a notation variant of SLU-PP-332 [11]

None of these notations distinguishes purity grade or supplier, so catalogue comparison should rely on the CAS number and a certificate of analysis rather than on spelling. The primary literature uses SLU-PP-332 exclusively [1,3,11].

Comparative evidence across the ERR ligand family

All findings below derive from cell-based assays or rodent models; no member of the family has been studied in humans.

Compound	Receptor profile	Reported model systems	Key reported observations
SLU-PP-332	Pan-agonist, ERRα-preferring [1]	C2C12 myotubes; C57BL/6J, DIO and ob/ob mice; TAC heart-failure mice	ERRα-dependent exercise-like gene program, increased treadmill endurance, type IIa fiber shift [1]; increased energy expenditure and fatty-acid oxidation with reduced fat mass in obese mice [3]; improved ejection fraction and reduced fibrosis after pressure overload [11]
SLU-PP-915	Pan-agonist, orally bioavailable [11]	TAC and MI heart-failure mice	Normalized fatty-acid and TCA/OXPHOS metabolite profiles, improved ejection fraction, ERRγ-dependent cardioprotection, induction of cardiomyocyte autophagy [11]
GSK4716	ERRβ/γ agonist [4]	Reporter assays; ERRγ LBD crystallography	PGC-1α-mimetic activation; selective over ERα/ERβ; defined the agonist-bound ERRγ conformation [4,10]
DY131 (GSK9089)	ERRβ/γ agonist [9]	Transient transfection assays	Selective activation of ERRβ/γ with no effect on ERRα or estrogen receptors [9]
XCT790	ERRα inverse agonist [8]	Reporter assays; cancer cell lines	Suppresses constitutive ERRα activity; off-target mitochondrial uncoupling and AMPK activation at nanomolar concentrations [8,12]

Subtype dependence differs by tissue

The skeletal-muscle phenotype of SLU-PP-332 — an exercise-like gene set including Ddit4, longer treadmill running and a shift toward oxidative type IIa fibers — was abolished in ERRα-null mice, establishing ERRα dependence [1]. In obese mice the same oxidative program was associated with increased energy expenditure and fatty-acid oxidation without a change in food intake [3]. In pressure-overload heart failure, by contrast, genetic studies identified ERRγ as the principal mediator of cardioprotection [11]. This tissue-specific subtype dependence is the stated rationale for pursuing pan-agonism rather than subtype selectivity in the SLU-PP series [1,11].

Limitations and research considerations

• No human data. Neither SLU-PP-332 nor any other synthetic ERR agonist has been evaluated in a registered clinical trial; all reported observations are from cell culture or rodents [1,3,11].
• Pharmacokinetics. SLU-PP-332 is reported to lack oral bioavailability, which motivated the design of SLU-PP-915 [11].
• Systemic ERR activation. ERRs are expressed in liver, kidney, brain and proliferating tissues; ERRα has been implicated in tumor-cell metabolism, and the long-term consequences of pan-ERR agonism have not been characterized [5].
• Tool-compound caveats. XCT790, the usual pharmacological control for ERRα, has documented ERRα-independent effects on mitochondrial coupling and AMPK, so loss-of-function comparisons should include genetic controls [12].
• Catalogue ambiguity. Identity should be confirmed by CAS number, mass spectrometry and HPLC purity rather than by product title.

Where to source for research

SLU-PP-332 is available as a research-grade small molecule from suppliers that also list research peptides — the origin of the "peptide" catalogue label. Short Chain Aminos lists ERR-pathway research compounds alongside its peptide range with lot-specific certificates of analysis. BioPep, Catalyst Research and Apex Research Services also carry research-use-only catalogues in this category. For any supplier, the certificate of analysis should report CAS 303760-60-3, the expected mass (290.3 g/mol) and HPLC purity. Our guide on how to evaluate research peptide suppliers applies equally to small-molecule research compounds.

Frequently asked research questions

What is SLU-PP-332?

SLU-PP-332 is a synthetic phenolic acyl hydrazone (C₁₈H₁₄N₂O₂, 290.3 g/mol) that acts as a pan-agonist of estrogen-related receptors ERRα, ERRβ and ERRγ. It was reported in 2023 by the Burris laboratory as a chemical probe that induces an ERRα-dependent exercise-like transcriptional program in mouse skeletal muscle [1,2].

Is the "slu pp 332 peptide" actually a peptide?

No. The molecule contains no amino acids and no peptide bonds; it is a small-molecule nuclear-receptor ligand derived from the GSK4716 acyl hydrazone scaffold. The word "peptide" in catalogue titles and queries such as slu-pp-332 peptide or slupp peptide reflects where suppliers list the compound, not its chemistry [1,2,4].

Are slupp332, sloop peptide and slupe 332 different compounds?

They are not. All are notation variants — concatenated, phonetic or mis-typed forms — of SLU-PP-332 (CAS 303760-60-3). The only distinct compound commonly confused with it is SLU-PP-915, the orally bioavailable successor reported in 2024 [2,11].

How does SLU-PP-332 differ from GSK4716 and DY131?

All three share a 4-hydroxybenzohydrazide core. GSK4716 and DY131 are selective ERRβ/γ agonists with negligible ERRα activity, whereas SLU-PP-332 carries a 2-naphthyl group that extends into the ERRα pocket and confers pan-agonism with ERRα preference (EC₅₀ ≈ 98 nM) [1,4,9].

What is SLU-PP-915?

SLU-PP-915 is a second-generation pan-ERR agonist produced by structure-based design to achieve oral bioavailability, which SLU-PP-332 lacks. In pressure-overload heart-failure mice it was associated with improved ejection fraction, reduced fibrosis and normalized cardiac fatty-acid metabolism, mediated principally by ERRγ [11].

Has SLU-PP-332 been studied in humans?

No. As of this review there are no registered clinical trials of SLU-PP-332 or any synthetic ERR agonist. All reported findings come from cell-based assays and mouse models, and the compound is supplied strictly as a research-use-only chemical probe [1,3,11].

Works Cited

1. Billon C, Sitaula S, Banerjee S, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(4):756-771. doi:10.1021/acschembio.2c00720. PMID 36988910.
2. National Center for Biotechnology Information. PubChem Compound Summary: SLU-PP-332 (CAS 303760-60-3). pubchem.ncbi.nlm.nih.gov/compound/Slu-PP-332.
3. Billon C, Schoepke E, Avdagic A, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. doi:10.1124/jpet.123.001733. PMID 37739804.
4. Zuercher WJ, Gaillard S, Orband-Miller LA, et al. Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRβ and ERRγ. J Med Chem. 2005;48(9):3107-3109. doi:10.1021/jm050161j. PMID 15857113.
5. Giguère V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev. 2008;29(6):677-696. doi:10.1210/er.2008-0017. PMID 18664618.
6. Huss JM, Torra IP, Staels B, Giguère V, Kelly DP. Estrogen-related receptor α directs peroxisome proliferator-activated receptor α signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 2004;24(20):9079-9091. doi:10.1128/MCB.24.20.9079-9091.2004. PMID 15456881.
7. Fan W, Evans RM. Exercise mimetics: impact on health and performance. Cell Metab. 2017;25(2):242-247. doi:10.1016/j.cmet.2016.10.022. PMID 27889389.
8. Busch BB, Stevens WC Jr, Martin R, et al. Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor α. J Med Chem. 2004;47(23):5593-5596. doi:10.1021/jm049334f. PMID 15509154.
9. Yu DD, Forman BM. Identification of an agonist ligand for estrogen-related receptors ERRβ/γ. Bioorg Med Chem Lett. 2005;15(5):1311-1313. doi:10.1016/j.bmcl.2005.01.025. PMID 15713377.
10. Wang L, Zuercher WJ, Consler TG, et al. X-ray crystal structures of the estrogen-related receptor-γ ligand binding domain in three functional states reveal the molecular basis of small molecule regulation. J Biol Chem. 2006;281(49):37773-37781. doi:10.1074/jbc.M608410200. PMID 16990259.
11. Xu W, Billon C, Li H, et al. Novel pan-ERR agonists ameliorate heart failure through enhancing cardiac fatty acid metabolism and mitochondrial function. Circulation. 2024;149(3):227-250. doi:10.1161/CIRCULATIONAHA.123.066542. PMID 37961903.
12. Eskiocak B, Ali A, White MA. The estrogen-related receptor α inverse agonist XCT 790 is a nanomolar mitochondrial uncoupler. Biochemistry. 2014;53(29):4839-4846. doi:10.1021/bi500737n. PMID 24999922.

Research use only. This article summarizes published preclinical literature for research reference. SLU-PP-332 and the other ERR ligands discussed are investigational chemical probes and are not for human or veterinary use. All content strictly for research reference.

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